Susceptibility Variations in Air Pollution Health Effects: Incorporating Neuroendocrine Activation

Abstract

Diverse host factors/phenotypes may exacerbate or diminish biological responses induced by air pollutant exposure. We lack an understanding of biological indicators of environmental exposures that culminate in a physiological response versus those that lead to adversity. Variations in response phenotype might arise centrally and/or at the local tissue level. In addition to genetic differences, the current evidence supports the roles of preexisting cardiopulmonary diseases, diabetes, diet, adverse prenatal environments, neurobehavioral disorders, childhood infections, microbiome, sex, and psychosocial stressors in modifying the susceptibility to air pollutant exposures. Animal models of human diseases, obesity, nutritional inadequacies, and neurobehavioral conditions have been compared with healthy controls to understand the causes of variations in susceptibility. Although psychosocial stressors have been associated with increased susceptibility to air pollutant effects, the contribution of neuroendocrine stress pathways in mediating these effects is just emerging. The new findings of neuroendocrine activation leading to systemic metabolic and immunological effects of air pollutants, and the potential contribution to allostatic load, emphasize the consideration of these mechanisms into susceptibility. Variations in susceptibility to air pollution health effects are likely to underlie host genetic and physiological conditions in concert with disrupted neuroendocrine circuitry that alters physiological stability under the influence of stressors.

Offspring susceptibility to metabolic alterations due to maternal high-fat diet and the impact of inhaled ozone used as a stressor

“…Ozone has been extensively studied for its pulmonary effects; however, more recently neurological and systemic effects have also been reported 8 . We have shown that similar to many non-chemical (psychosocial) stressors 9 , a single acute ozone inhalation produces a myriad of changes in metabolic and immunological processes through sympathetic and hypothalamic neuroendocrine stress pathway activation 10,11 . Thus, acute ozone exposure as a stressor may alter a broad spectrum of homeostatic processes, which in susceptible individuals may contribute to exacerbation of metabolic disease.…”

Does ozone inhalation cause adverse metabolic effects in humans? A systematic review

“…In addition, repeated episodic exposures may result in an attenuation of the ozone-induced effects, possibly due to the initiation of an adaptive response. Some evidence indicates that neurohumoral sympathetic modulation may be involved in the mechanism of ozoneinduced fasting hyperglycemia and glucose intolerance (Bass et al 2013;Kodavanti et al 2015;Kodavanti 2019). In particular, the hypothesis suggests that ozone induces a neuroendocrine stress response, activating the hypothalamic-pituitaryadrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes, which can lead to increased circulating epinephrine and glucocorticoids, including corticosterone, although the available data are not consistent (Miller et al 2015;Snow et al 2018;Henriquez et al 2019Henriquez et al , 2020.…”

“…In addition, exacerbation of ozone-induced systemic effects has been reported in rats treated with b 2 -adrenergic and glucocorticoid receptor agonists, whereas these effects are mitigated in rats treated with adrenergic and glucocorticoid receptor antagonists (Snow et al 2018;Henriquez et al 2019Henriquez et al , 2020. Emerging evidence suggests that the tissue distribution of these receptors, along with the presence of individual variability, may represent a critical factor in these specific ozone-induced metabolic effects (Kodavanti 2019). Although some data report that ozone has been shown to activate the HPA and SAM axes, the initiating events of autonomic activation remain unclear, particularly the role of vagal sensory nerves and/or circulating mediators that may act on different brain regions, such as the hypothalamus.…”

Adrenergic and Glucocorticoid Receptors in the Pulmonary Health Effects of Air Pollution

“…Although local pulmonary cellular changes have been characterized extensively with acute exposure to different pollutants, the mechanisms by which the immune response is activated and immune cells are recruited from lymphoid organs, matured, and extravasated to the site of injury are not well understood. Our recent studies have shown that the adrenergic and glucocorticoid pathways are involved in pulmonary vascular leakage and inflammatory response induced by irritant pollutants, such as ozone [14,81,82]. In light of recent research into the marked effects of air pollutants on the brain [7,[82][83][84], and the involvement of the neuroendocrine system with increased adrenal-derived stress hormones [85], it is conceivable that AR and GR activation are involved in the health effects of air pollution.…”

“…Our recent studies have shown that the adrenergic and glucocorticoid pathways are involved in pulmonary vascular leakage and inflammatory response induced by irritant pollutants, such as ozone [14,81,82]. In light of recent research into the marked effects of air pollutants on the brain [7,[82][83][84], and the involvement of the neuroendocrine system with increased adrenal-derived stress hormones [85], it is conceivable that AR and GR activation are involved in the health effects of air pollution. Understanding the roles of these receptors may explain how a pulmonary inflammatory response is generated after exposure to air pollutants, why there is tolerance or adaptation to this initial pulmonary response, how individuals with psychosocial disorders and altered neuroendocrine regulation may be more susceptible, and what systemic mediators are critical for initial injury and inflammation.…”